Neurologic Conditions

Many neurologic conditions present during the neonatal period. The neonatal neurologic exam encompasses primitive reflexes with expected changes in these reflexes over time.

This section covers the following neonatal neurologic conditions:

• Seizures

• Perinatal Asphyxia

• Intracranial Hemorrhage

• Retinopathy of Prematurity

Seizures

Neonatal seizures can be subtle, caused by a variety of etiologies, and challenging to differentiate from normal newborn behaviors (particularly in the preterm infant). A high index of suspicion is necessary to identify subtle seizures.

The presentation of neonatal seizures can include the following:

• tonic movements

• clonic movements

• myoclonic movements

• autonomic changes

Differential Diagnosis

The differential diagnosis of neonatal seizures should be broad and include:

• hypoxic-ischemic encephalopathy

• metabolic or other genetic disorders

• infectious etiologies

• electrolyte abnormalities

• intracranial hemorrhage

• withdrawal from maternal medications or drugs of abuse

• benign etiologies (including myoclonic jerks, benign sleep myoclonus, fifth-day fits)

Evaluation

An amplitude integrated electroencephalogram (aEEG) and video EEG can be used to evaluate brain activity for electrical evidence of seizures if suspected. Further workup for neonatal seizures includes the following:

• metabolic disorder: electrolytes (specifically glucose, sodium, calcium, and magnesium), serum amino acids, and urine organic acids (with an ammonia level if an inborn error of metabolism is suspected). It is important to review the newborn blood spot screen for any evidence of inborn errors of metabolism. Additional molecular genetic testing may be indicated.

• infectious etiology: sepsis evaluation, including lumbar puncture for potential meningitis

• intracranial hemorrhage: head ultrasounds can be performed at the bedside

Management

If seizures are associated with hypoglycemia, a metabolic disturbance, or infection, the underlying condition should be treated along with the seizure activity itself. First line maintenance medication for neonatal seizures is phenobarbital. Other medications include fosphenytoin, benzodiazepines, and levetiracetam.

Perinatal Asphyxia

Perinatal asphyxia is caused by a lack of oxygen to the infant due to a hypoxic or ischemic event that occurs immediately before, during, or after birth. Events occurring around the time of delivery, such as uterine rupture, feto-maternal hemorrhage, or significant compromise of blood flow, can lead to organ failure and neurologic injury (hypoxic-ischemic encephalopathy [HIE]) due to lack of oxygen. Other systemic effects of perinatal asphyxia include respiratory distress, pulmonary hypertension, and liver, myocardial, and renal dysfunction.

Diagnosis

Diagnosis of perinatal asphyxia necessitates a prenatal history of complications that could decrease oxygen delivery to the infant and lead to acidemia, which can be assessed by analyzing cord blood gases. The lack of oxygen can result in low Apgar scores, indicating the need for increased delivery room resuscitative efforts. A postnatal exam consistent with a neurologically depressed infant (i.e., inactive, poor reflexes, low tone) raises concern for neonatal encephalopathy as a consequence of asphyxia. The phenomenon of neonatal encephalopathy following fetal distress was first described in 1976. Follow-up studies have identified associated exam findings.

Clinical exam: It is important to look for signs of neonatal encephalopathy in the first several hours after delivery in order to initiate therapy for presumed perinatal asphyxia. Although some institutions use their own scoring rubric, the main components of the exam are as follows:

• tone of the infant (increased or decreased)

• degree of spontaneous movement

• vital sign instability

• presence or absence of reflexes

• evidence of seizure activity (a video EEG may demonstrate seizures)

Treatment

In the early 2000s, different methods of lowering an infant’s body temperature to prevent further toxicity to brain cells were found to improve outcomes at discharge and later neurodevelopmental outcomes in infants with signs of neonatal encephalopathy. The use of therapeutic hypothermia has been widely adopted since that time. Most institutions use whole body cooling rather than isolated head cooling. The goal of neonatal therapeutic hypothermia is to cool the infant’s core body temperature to 33-34°C for 72 hours and then slowly rewarm. After rewarming, an MRI is performed, and the infant is typically followed by Neurology as an outpatient. Cooling should be initiated <6 hours after delivery for best outcomes.

Inclusion criteria for cooling include the following:

• age at birth of ≥35 weeks gestation and weight ≥2000 grams

• fetal or neonatal distress during delivery

• moderate-to-severe neonatal encephalopathy on physical exam

Intracranial Hemorrhages

Premature infants are at increased risk for intracranial hemorrhage (ICH), including intraventricular hemorrhage (IVH) due to friable blood vessels located in the germinal matrix. ICH and IVH may affect long-term neurodevelopmental outcomes. Infants <32 weeks’ gestation and weighing <1500 grams are at highest risk for IVH, although incidence generally increases with decreasing gestational age and term infants can also have IVH.

(Source: Injuries of extracranial, cranial, intracranial, spinal cord, and peripheral nervous system structures. In: Volpe JJ, ed. Neurology of the Newborn. 4th ed. Philadelphia, PA: WB Saunders; 2001:813. Elsevier 2001.)

Screening

Most institutions perform serial head ultrasounds as part of routine screening for IVH in infants <32 weeks' gestation or weighing <1500 grams at birth.

Management

If IVH is identified on screening head ultrasound, more frequent imaging is indicated to assess if the bleed is progressing or stabilized. Evidence of ventricular dilatation requires consultation with both Neurology and Neurosurgery for possible interventions (including shunts or drains) to remove excess cerebral spinal fluid (CSF).

Retinopathy of Prematurity

The retina does not reach full vascularization until 36-40 weeks gestation. Premature infants are at risk for abnormal vascular growth of the retina. Retinopathy of prematurity(ROP) can affect very preterm infants and infants with severe illness and prolonged exposure to hyperoxia.

(Source: Mechanisms and Management of Retinopathy of Prematurity. N Engl J Med 2012.)

Screening

Premature infants <30 weeks’ gestation or weighing <1500 grams at birth and infants who remain severely ill during the NICU course should be screened for ROP. If abnormalities are found, follow-up exams should be performed at least every 2 weeks.

Classification

ROP is classified according to zone, stage, extent, and plus or no plus disease:

• Zone refers to the area of the retina affected during growth and development.

• Stage refers to the severity of disease.

• Extent is reported in clock hours and indicates the areas of the retina affected.

• Plus disease refers to the vascularity of the retina and more aggressive disease.

Management

Treatment for ROP depends on the extent of progression. Laser therapy is used to prevent further vessel growth and retinal detachment. In the past, cryotherapy was used often, especially in the presence of vitreous hemorrhage, which prevents adequate delivery of laser therapy. Anti-vascular endothelial growth factor (anti-VEGF) injections to the eye can help prevent aberrant vessel growth.

Neonatal Abstinence Syndrome

Neonatal abstinence syndrome (NAS) occurs when an infant is exposed to maternal medications and experiences symptoms of withdrawal after birth. NAS is most often associated with maternal opioid exposure but can also result from exposure to nicotine or SSRI medications. Maternal polypharmacy increases the risk for NAS. In cases of isolated opioid withdrawal, the term neonatal opioid withdrawal syndrome (NOWS) is used.

Presentation

Infants with NAS can present with a variety of symptoms including difficulty feeding, sleeping and settling, tremors, sneezing, yawning, loose stools, and vomiting. The standard of care has been to assess infants using the Modified Finnegan Score to determine if pharmacologic treatment should be considered. A score >8 on three consecutive assessments or a score >12 on two consecutive assessments indicates pharmacologic treatment should be considered. The Eat, Sleep, Console assessment is a newer approach that has been shown to reduce pharmacologic treatment of neonatal opioid withdrawal syndrome. This approach assesses whether the infant has poor eating due to NAS, sleeps <1 hour after a feeding due to NAS, or is unable to be consoled within 10 minutes due to NAS, and encourages parents to be involved in intervening with nonpharmacologic measures before medications are used.

Management

Nonpharmacologic treatment is the first-line therapy for NAS, including breastfeeding when safely indicated and placing the infant in a quiet, dark room and swaddling. If these interventions fail to reduce NAS scores, pharmacologic treatments include morphine, methadone, and buprenorphine. Some institutions use as needed (PRN) dosing of morphine or methadone to treat infant withdrawal at the peak of symptoms (typically 3-5 days postnatally). Phenobarbital and clonidine can be used as adjunctive medications in some circumstances.